Recently, it has been reported that particular fluorescein derivatives, that per se have almost no fluorescent property, readily react with nitrogen monoxide under a neutral pH condition to provide a triazole compound having a strong fluorescence intensity, and the triazole derivative can emit intense fluorescence at a wavelength of around 515 nm under excitation light at a long wavelength of around 495 nm (Kojima et al., the 16th Medicinal Chemistry Symposium, the 5th Annual Meeting of the Pharmaceutical Chemistry Section, the Lecture Abstracts, pp. 166-167, Subject No. 2-P-26, published by the Pharmaceutical Society of Japan, Oct. 23, 1996). When these fluorescein derivatives are used as an agent for nitrogen monoxide measurement, the excitation light can be easily cut off with a fluorescence filter provided on an ordinary fluorescence microscope, and intracellular nitrogen monoxide concentration can be conveniently measured by measuring fluorescence in individual cells. However, lights in the visible region having a wavelength of around 500 nm are significantly absorbed by living tissues, and therefore, they are disadvantageous for in vivo imaging of nitrogen monoxide, and they also have a problem that regions for which imaging can be performed are limited to those around the epidermis. For this reason, it is desired to develop a probe which exhibits high transmission for living tissues and can be excited with a near-infrared light of a wavelength around 650 to 950 nm.
Zinc is an essential metallic element that is present in the human body in the largest amount next to iron, and most zinc ions in cells strongly couple to proteins and are involved in the maintenance of structures of proteins or in the expression of functions of the proteins. Various reports have also been made on the physiological role of free zinc ions, which are present in cells in a very small quantity (generally at a level of μM or lower). In particular, zinc ions are considered to be deeply involved in apoptosis, which is one of cell death processes, and it has also been reported that zinc ions accelerate senile plaque formation in Alzheimer's disease, for example. As for zinc ions, fluorescent zinc probes described in International Patent Publication WO01/62755 have been proposed as fluorescent probes for zinc which can measure zinc ions with high sensitivity and cause no cell injury
[Patent document 1] Japanese Patent No. 3200024
[Patent document 2] International Patent Publication WO01/62755